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Itinerant dynamics of the brain generates transient and recurrent spatiotemporal patterns in neuroimaging data. Characterizing metastable functional connectivity (FC) – particularly at rest and using functional magnetic resonance imaging (fMRI) – has shaped the field of dynamic functional connectivity (DFC). Mainstream DFC research relies on (sliding window) correlations to identify recurrent FC patterns. Recently, functional relevance of the  instantaneous phase synchrony  (IPS) of fMRI signals has been revealed using imaging studies and computational models. In the present paper, we identify the repertoire of whole-brain inter-network IPS states at rest. Moreover, we uncover a hierarchy in the temporal organization of IPS modes. We hypothesize that connectivity disorder in schizophrenia (SZ) is related to the (deep) temporal arrangement of large-scale IPS modes. Hence, we analyze resting-state fMRI data from 68 healthy controls (HC) and 51 SZ patients. Seven resting-state networks (and their sub-components) are identified using spatial independent component analysis. IPS is computed between subject-specific network time courses, using analytic signals. The resultant phase coupling patterns, across time and subjects, are clustered into eight IPS states. Statistical tests show that the relative expression and mean lifetime of certain IPS states have been altered in SZ. Namely, patients spend (45%) less time in a globally coherent state and a subcortical-centered state, and (40%) more time in states reflecting anticoupling within the cognitive control network, compared to the HC. Moreover, the transition profile (between states) reveals a deep temporal structure, shaping two metastates with distinct phase synchrony profiles. A metastate is a collection of states such that within-metastate transitions are more probable than across. Remarkably, metastate occupation balance is altered in SZ, in favor of the less synchronous metastate that promotes disconnection across networks. Furthermore, the trajectory of IPS patterns is less efficient, less smooth, and more restricted in SZ subjects, compared to the HC. Finally, a regression analysis confirms the diagnostic value of the defined IPS measures for SZ identification, highlighting the distinctive role of metastate proportion. Our results suggest that the proposed IPS features may be used for classification studies and for characterizing phase synchrony modes in other (clinical) populations.

Deep Temporal Organization of fMRI Phase Synchrony Modes Promotes Large-Scale Disconnection in Schizophrenia